We are following 50,844 US and Puerto Rican women who were between the ages of 35 and 74 and had a sister with breast cancer but did not have breast cancer themselves when they joined the study between 2003 and 2009. At enrollment, data on potential risk factors and current health status were collected using computer assisted telephone interviews and mailed questionnaires. Blood, urine, and environmental samples were collected in a home visit and banked for future use in nested studies of women who develop breast cancer (or other diseases) and a sample of those who don't. The cohort is tracked annually for changes in vital status and major health outcomes. Detailed follow-up questionnaires on health outcomes, environmental and lifestyle exposures, and special topics are completed every 2-3 years. Medical records and tumor tissue (for breast cancer cases) are retrieved for those who develop cancer or other conditions of interest. The first Sister Study follow-up survey was completed in June 2012; responses were obtained from 48,090 women for a response rate of 95%. The second detailed follow-up (January 2012 to 2014) was completed with better than 90% response. The third comprehensive follow-up will finish shortly with an overall 92% response. Planning is underway for the next comprehensive follow-up. In 2014-2015 we repeated the collection of biological and environmental samples from women diagnosed with breast cancer since enrollment and a random sample of the cohort. Of approximately 3,800 participants invited, samples were collected from 2,436 (63%) including 1,229 women who had been diagnosed with breast cancer. Repeat samples will allow us to explore changes in biomarkers and exposures over time and in relation to breast cancer diagnosis and treatment. More than 2,500 women have reported a diagnosis of breast cancer or DCIS/LCIS. As expected, women in the cohort have, on average, more than twice the breast cancer risk as other US women. The ratio of observed to expected cases is greatest for women who also have a mother with breast cancer and for those whose sisters were younger at diagnosis. All breast cancer and ovarian cancer cases and a random sample of the cohort have been genotyped as part of the multi-study Oncoarray project. We also generated data on 450,000 CpGs for the same 2000 breast cancer cases and 2000 non cases to evaluate methylation patterns in relation to breast cancer and in relation to exposures of interest. Sister Study data have been included in several collaborative analyses (pooling projects) from the oncoarray project whose findings on potentially novel loci in ovarian cancer, estrogen receptor negative breast cancer, and common type breast cancer have been submitted for publication. Two projects from the Sister Study addressed potential controversies in breast and ovarian cancer. In one study, (Wilson et all, 2016) we showed that the use of calcium channel blocking drugs was not associated with increased risk, despite an earlier report from a retrospective study. The finding is good news given the large numbers of women taking these drugs for treatment of hypertension. We similarly found that application of talc-containing powders in the genital area was not associated with increased risk for ovarian cancer in this cohort. These findings differ from those of many retrospective and a few other prospective studies that have raised public health concerns about the use of talc. On the other hand, we found that douching was associated with a nearly two-fold increase in risk for ovarian cancer. We carried out several analyses related to Antimullerian hormone (AMH). AMH is a marker of ovarian reserve that is thought to be more stable than other hormone markers. We found that higher levels of AMH were associated with higher breast cancer risk among women who were premenopausal when they joined the Sister study. We also found that lower AMH levels were associated with sources of indoor heating, including burning wood and use of a residential indoor stove or fireplace. AMH levels were also lower in smokers, consistent with prior evidence of earlier menopause in smokers. With co-investigators at the University of Washington, we geocoded participant addresses and linked these to information on air pollution levels. We recently found that while there was no overall link between air pollution and breast cancer, air pollution was associated with increased risk for hormone receptor positive breast cancer in this cohort. Other recent findings from the Sister Study include a general lack of support for an association between childhood and adolescent pesticide exposure and breast cancer risk, and lack of support for a benefit of use of complementary and alternative medicines in the prevention of breast cancer, even though use was higher in this cohort than in other populations. On the other hand, we did find that use of nonsteroidal anti-inflammatory drugs overall, and of aspirin was associated with reduced risk of breast cancer among premenopausal women. We also reported that central adiposity was related to breast cancer risk in both pre-and postmenopausal women and in current work we are further exploring the impact of metabolic syndrome on risk for breast cancer and other diseases. Finally, we also used our data to carry out research on other diseases of relevance to women, including the autoimmune diseases rheumatoid arthritis and systemic lupus erythematosus. The Sister Study is collaborating with researchers from the Division of Cancer Prevention and Control at the Centers for Disease Control and Prevention (CDC) to study quality of life in breast cancer survivors. A survey of approximately 20,000 Sister Study participants in 2012 focused on the impact of having a sister with breast cancer. A second survey, completed in May 2013, involved women diagnosed with breast cancer and included topics that are of particular interest to younger women such as body image, work-life balance, and fertility as well as questions related to breast cancer care and quality of life. Together, these surveys will increase our understanding of the impact of cancer on the lives of breast cancer survivors and their families and provide information that will help identify factors related to healthy living after diagnosis. Current analyses focus on receipt of and satisfaction with prophylactic mastectomy, whether breast MRI is being used appropriately for high risk women, neurocognitive symptoms following chemotherapy, and behavioral change following breast cancer diagnosis. The Sister Study participates in the NCI-sponsored Cohort Consortium and has contributed cases a and data to studies of head and neck, gallbladder and ovarian cancers, allowing us to contribute to research on conditions we are not able to address on our own due to sample size constraints. For example, we contributed to an analysis of risk factors for specific histologic subtypes of ovarian cancer. We are leading a new Consortium project on pregnancy-associated breast cancer and co-directing a Consortium study on risk factors for pre-menopausal breast cancer with collaborators from the UK. To date 20 cohorts have joined this effort.